Pregnancy outcome among patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors

目的 观察接受酪氨酸激酶抑制剂( TKI)治疗的慢性髓系白血病(CML)患者的生育结果.方法 回顾性收集接受TKI治疗的CML患者或其配偶妊娠、生育的相关信息.结果 2例年轻女性患者和10例中位年龄为33.5(26 ～46)岁的男性患者的配偶妊娠,并生产了12名婴儿.2例女性患者在伊马替尼治疗90和91个月时发现意外怀孕,1例仅停药1个月、1例妊娠全程和产后哺乳半年期间持续服用伊马替尼.10例男性患者中,7例在伊马替尼中位治疗60( 11 ～96)个月时、3例在达沙替尼中位治疗3(2.5～7.O)个月时,发现其配偶妊娠.所有患者生育前后疾病均处于血液学、细胞遗传学或分子学缓解状态.12名婴儿中,除1名早产、低体重并有尿道下裂的畸形外(出生后手术修复),其余11名均为足月生产,未见器官畸形.目前,12例患者子女生长发育正常,中位年龄17.5(3～101)个月.结论 在TKI治疗期间,女性CML患者和男性CML患者的配偶均可产出正常婴儿,但也有发生先天畸形的可能.建议育龄期女性患者在TKI治疗中应该有效避孕,并避免哺乳.当患者发现意外妊娠后,应咨询医生,权衡服药与妊娠的风险与收益.男性患者在服用伊马替尼期间无须避孕.To observe the pregnancy outcome among patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs).Data associated with pregnancy, delivery and neonate from the patients or patient's spouse who conceived while receiving TKIs were collected retrospectively.Two young female patients (who had been on imatinib therapy for 90 and 91 months, respectively) and spouses of 10 male patients (involving 7 patients who had received imatinib for a median of 60 months and 3 who had received dasatinib for 2.5 months to 7 months, respectively) with median age of 33.5 years (range 26 - 46 years) conceived and gave birth to 12 babies. One woman took imatinib throughout her pregnancy except one month. The other one took imatinib throughout her pregnancy and had breast-fed while on imatinib therapy for nearly half a year postpartum. Among the 12 babies, one was born prematurely with low birth weight and hypospadias (surgical repair after birth), the others were all healthy with no congenital defects. The median age of the children at the date of this report is 17.5 months (range 3 to 101 months), and they all have a normal pattern of growth and development.Conception among patients with CML while receiving TKIs may result in normal pregnancies. The possible effects of TKIs on birth abnormalities cannot be ruled out. It is recommended that childbearing female patients should be advised to practice adequate methods of contraception and should not breast-feed while on TKIs therapy. In cases of accidental pregnancy, risk/benefit evaluations must be carried out carefully on an individual basis. No special precautions apply for male patients being treated with imatinib.国家重大新药创制专项; 国家自然科学基金杰出青年基金PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)016-93